2008
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety
Yang X, Izadi H, Coleman AS, Wang P, Ma Y, Fikrig E, Anguita J, Pal U. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety. Microbes And Infection 2008, 10: 1300-1308. PMID: 18725314, PMCID: PMC2648844, DOI: 10.1016/j.micinf.2008.07.029.Peer-Reviewed Original ResearchConceptsB mutantsWild-type B. burgdorferiP38 MAP kinase pathwayMAP kinase pathwayHuman synovial cellsSynovial cellsProtein moietyP38 MAP kinaseNF-kappaBLyme arthritisB operonKinase pathwayMAP kinaseRecombinant BmpAPro-inflammatory cytokines TNF-alphaCultured human synovial cellsLipopolysaccharide inhibitorMutantsCytokines TNF-alphaHost inflammatory responsePro-inflammatory responseCytokine responsesIL-1betaTNF-alphaInflammatory response
2007
Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis
Pal U, Wang P, Bao F, Yang X, Samanta S, Schoen R, Wormser GP, Schwartz I, Fikrig E. Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis. Journal Of Experimental Medicine 2007, 205: 133-141. PMID: 18166585, PMCID: PMC2234379, DOI: 10.1084/jem.20070962.Peer-Reviewed Original ResearchConceptsLyme arthritisMouse jointsB. burgdorferi antigensBurgdorferi-infected miceSevere arthritisSpirochete numbersArthritisHost responseLyme diseaseAffinity-purified antibodiesBorrelia burgdorferiChain reactionMiceOriginal phenotypeBasic membrane proteinMutant spirochetesGene expressionJointsInflammationPathogenesisAntigenDiseaseB. burgdorferi gene expression
2002
Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis
Anguita J, Samanta S, Ananthanarayanan SK, Revilla B, Geba GP, Barthold SW, Fikrig E. Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. Pathogens And Disease 2002, 34: 187-191. PMID: 12423770, PMCID: PMC4307933, DOI: 10.1111/j.1574-695x.2002.tb00623.x.Peer-Reviewed Original ResearchConceptsJoint inflammationCOX-2B. burgdorferi-specific antibodyBurgdorferi-specific antibodiesOnset of arthritisDegree of inflammationNoninfectious inflammatory diseasesCyclooxygenase-2 activityCOX-2 activityB. burgdorferiCOX-2 gene expressionMurine Lyme arthritisSpecific inhibitionLyme arthritisCytokine responsesInfectious arthritisRheumatoid arthritisInfected miceInflammatory diseasesInducible isoformMurine jointsArthritisInflammationMRNA expressionLyme diseaseMurine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity
Anguita J, Barthold SW, Persinski R, Hedrick MN, Huy CA, Davis RJ, Flavell RA, Fikrig E. Murine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity. The Journal Of Immunology 2002, 168: 6352-6357. PMID: 12055252, PMCID: PMC4309983, DOI: 10.4049/jimmunol.168.12.6352.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialArthritis, InfectiousBorrelia burgdorferiCD4-Positive T-LymphocytesCell LineEnzyme ActivationInflammationInterferon-gammaLyme DiseaseMAP Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhagocytesPhosphorylationProtein-Tyrosine KinasesReceptors, InterferonConceptsProinflammatory cytokine productionCytokine productionT helper type 1 responsePhagocytic cellsDevelopment of arthritisPotential new therapeutic approachType 1 responseInfection of miceExperimental murine modelMurine Lyme arthritisNew therapeutic approachesLyme arthritis developmentTreatment of inflammationCytokine burstArthritis developmentJoint inflammationLyme arthritisNF-kappa BProinflammatory cytokinesTNF-alphaT cellsMurine modelTherapeutic approachesP38 MAP kinaseSpecific Abs
2001
Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis
Thomas V, Anguita J, Barthold S, Fikrig E. Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis. Infection And Immunity 2001, 69: 3359-3371. PMID: 11292759, PMCID: PMC98295, DOI: 10.1128/iai.69.5.3359-3371.2001.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisLyme arthritisDual infectionBacterial burdenImmune responseTumor necrosis factor-alpha levelsB. burgdorferiElevated IL-6 levelsNecrosis factor-alpha levelsGranulocytic ehrlichiosisIL-6 levelsAgent of HGEMurine immune responseBorrelia burgdorferiTick-borne illnessMurine Lyme arthritisSevere Lyme arthritisCoinfection of miceIFN-gamma receptor expressionInfected miceInterleukin-12Receptor expressionGamma interferonArthritisPathogen burden
1999
Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists
Anguita J, Barthold S, Samanta S, Ryan J, Fikrig E. Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists. The Journal Of Infectious Diseases 1999, 179: 734-737. PMID: 9952389, DOI: 10.1086/314613.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAnti-Inflammatory AgentsArthritis, InfectiousFemaleHumansInflammationInterferon-gammaInterleukin-11Interleukin-12Interleukin-4Lyme DiseaseMiceMice, Inbred C3HMyocarditisNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsRNA, MessengerTranscription, GeneticConceptsMurine Lyme diseaseIL-11Potent anti-inflammatory propertiesInducible nitric oxide synthaseLyme diseaseMurine Lyme carditisAnti-inflammatory actionRole of interleukinAnti-inflammatory propertiesNitric oxide synthaseInnate immune responseB. burgdorferi-infected miceBurgdorferi-infected miceLyme carditisCardiac inflammationLyme arthritisIL-12Less arthritisIL-4Oxide synthaseBlocking antibodiesImmune responseControl animalsInterleukin-11Borrelia burgdorferiThe Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis
Akin E, McHugh G, Flavell R, Fikrig E, Steere A. The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis. Infection And Immunity 1999, 67: 173-181. PMID: 9864212, PMCID: PMC96293, DOI: 10.1128/iai.67.1.173-181.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupChildChild, PreschoolFemaleHumansImmunoglobulin GLipoproteinsLongitudinal StudiesLyme DiseaseMaleMiddle AgedSeverity of Illness IndexConceptsAntibody responseIgG antibodiesEarly arthritisLyme arthritisIgG responsesEarly infectionDuration of arthritisChronic Lyme arthritisIgG antibody responseSerial serum samplesBorrelia burgdorferi proteinsSubsequent arthritisB. burgdorferi proteinsSurface protein CC-terminal epitopeImmune responseArthritisSubsequent severityNatural historyLyme diseasePatientsSerum samplesImmunoglobulin GProtein CInfection
1998
Borrelia burgdorferi-Infected, Interleukin-6-Deficient Mice Have Decreased Th2 Responses and Increased Lyme Arthritis
Anguita J, Rincón M, Samanta S, Barthold S, Flavell R, Fikrig E. Borrelia burgdorferi-Infected, Interleukin-6-Deficient Mice Have Decreased Th2 Responses and Increased Lyme Arthritis. The Journal Of Infectious Diseases 1998, 178: 1512-1515. PMID: 9780277, DOI: 10.1086/314448.Peer-Reviewed Original ResearchConceptsIL-6-deficient miceLyme arthritisT cellsCell responsesCD4 T cell responsesT helper cell responsesInterleukin-6-deficient miceHelper cell responsesLess IL-4CD4 T cellsEffector Th2 cellsT cell responsesBorrelia burgdorferiNaive T cellsMurine Lyme arthritisDays of infectionJoint inflammationTh2 responsesArthritis incidenceIgG2b levelsC57BL/6 miceIL-6Th2 phenotypeIL-4Th2 cellsDifferential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis
Fikrig E, Feng W, Aversa J, Schoen R, Flavell R. Differential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis. The Journal Of Infectious Diseases 1998, 178: 1198-1201. PMID: 9806060, DOI: 10.1086/515684.Peer-Reviewed Original ResearchConceptsLyme arthritisLyme diseaseHuman infectionsPhase III clinical trialsMurine Lyme borreliosisRNA polymerase chain reactionErythema migrans biopsiesErythema migransProtective immunityClinical trialsVaccine candidatesTissue specimensLyme borreliosisPatientsGene expressionBorrelia burgdorferiDiseaseFirst direct demonstrationB. burgdorferiChain reactionArthritisInfectionBorrelia burgdorferi genesOspAB. burgdorferi gene expression
1997
Ablation of interleukin-12 exacerbates Lyme arthritis in SCID mice
Anguita J, Samanta S, Barthold SW, Fikrig E. Ablation of interleukin-12 exacerbates Lyme arthritis in SCID mice. Infection And Immunity 1997, 65: 4334-4336. PMID: 9317045, PMCID: PMC175621, DOI: 10.1128/iai.65.10.4334-4336.1997.Peer-Reviewed Original ResearchB7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis
Anguita J, Roth R, Samanta S, Gee RJ, Barthold SW, Mamula M, Fikrig E. B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis. Infection And Immunity 1997, 65: 3037-3041. PMID: 9234751, PMCID: PMC175428, DOI: 10.1128/iai.65.8.3037-3041.1997.Peer-Reviewed Original ResearchConceptsLyme arthritisMurine Lyme arthritisB7-1Monoclonal antibodiesCostimulatory moleculesB7-2Immune responseInterleukin-4C3H/HeN miceB7-2 costimulatory moleculesExperimental Lyme arthritisB7-2 expressionMurine Lyme borreliosisDegree of arthritisBorrelia burgdorferi infectionSplenocyte proliferative responseDose-dependent increaseHost immune responseT cell differentiationIL-10Antibody levelsIL-12HeN miceBurgdorferi infectionProliferative responseLyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015
Fikrig E, Barthold S, Chen M, Tao H, Ali-Salaam P, Bockenstedt L, Flavell R. Lyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015. The Journal Of Infectious Diseases 1997, 175: 1000-1003. PMID: 9086169, DOI: 10.1086/513958.Peer-Reviewed Original ResearchConceptsTransgenic miceLyme borreliosisC3H/HeN miceTolerance of miceSurface protein ABorrelia burgdorferi outer surface protein ASignificant arthritisOuter surface protein ALyme arthritisProtective immunityNontransgenic littermatesHeN miceOspA antibodiesDisease pathogenesisMiceArthritisB. burgdorferi N40OspABorreliosisCellular responsesProtein AResponseImmunizationPathogenesisLittermatesTemporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host.
Das S, Barthold SW, Giles SS, Montgomery RR, Telford SR, Fikrig E. Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. Journal Of Clinical Investigation 1997, 99: 987-995. PMID: 9062357, PMCID: PMC507907, DOI: 10.1172/jci119264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupElectrophoresis, Gel, Pulsed-FieldEnzyme-Linked Immunosorbent AssayFemaleFlagellinFluorescent Antibody Technique, IndirectGene Expression Regulation, BacterialHumansImmunizationImmunization, PassiveImmunoblottingIxodesLipoproteinsLyme DiseaseMiceMice, Inbred C3HPlasmidsPolymerase Chain ReactionRecombinant ProteinsRNA, MessengerTime FactorsConceptsInfected miceHumoral responseLate-stage Lyme diseaseMarkers of infectionCourse of diseaseMurine Lyme borreliosisB. burgdorferiB. burgdorferi infectionHuman humoral responseIxodes dammini ticksBurgdorferi-infected miceLyme arthritisActive immunizationMammalian hostsPassive transferBurgdorferi infectionC3H miceMurine infectionDay 14P21 antibodyP21 expressionLyme borreliosisLyme diseaseMiceInfection
1996
Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.
Bockenstedt LK, Fikrig E, Barthold SW, Flavell RA, Kantor FS. Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice. The Journal Of Immunology 1996, 157: 5496-502. PMID: 8955199, DOI: 10.4049/jimmunol.157.12.5496.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesEpitope MappingFemaleImmunization, PassiveImmunoglobulin GInterleukin-4LipoproteinsLymphocyte ActivationMiceMice, Inbred C3HMolecular Sequence DataPeptidesT-LymphocytesVaccines, SyntheticConceptsT cell epitopesCell epitopesPhase III efficacy studiesTick-borne spirochete Borrelia burgdorferiTreatment-resistant Lyme arthritisT cell responsesSurface protein AB-cell epitopesOuter surface protein ALyme arthritisChallenge infectionIgG productionN-terminal epitopeT cellsMultisystem disorderMurine modelSpirochete Borrelia burgdorferiSubunit vaccineEfficacy studiesCell responsesRecombinant vaccineLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
1995
An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies.
Fikrig E, Liu B, Fu LL, Das S, Smallwood JI, Flavell RA, Persing DH, Schoen RT, Barthold SW, Malawista SE. An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies. The Journal Of Immunology 1995, 155: 5700-4. PMID: 7499856, DOI: 10.4049/jimmunol.155.12.5700.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupFemaleFrameshift MutationHumansLipoproteinsLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataProtein BindingSynovial FluidConceptsSurface protein AOuter surface protein ASynovial fluidChronic Lyme arthritisSynovial fluid samplesSeparate time pointsImmune effectivenessLyme arthritisPassive immunizationProtective antibodiesHuman infectionsHuman AbsProtein ATime pointsNatural infectionInfectionBorrelia burgdorferiMiceOnly factorHuman hostFluid samplesOspAInfected hostHuman materialMicrobial persistenceLyme Disease in Human DR4Dw4-Transgenic Mice
Feng S, Barthold S, Bockenstedt L, Zaller D, Fikrig E. Lyme Disease in Human DR4Dw4-Transgenic Mice. The Journal Of Infectious Diseases 1995, 172: 286-289. PMID: 7797933, DOI: 10.1093/infdis/172.1.286.Peer-Reviewed Original ResearchConceptsDR4 transgenic miceChronic Lyme arthritisLyme arthritisGroups of miceHigh antibody titersHLA-DR4 allelesB. burgdorferiControl miceMajor histocompatibility complex class II genesAntibody titersArthritisOuter surface proteinsClass II genesLyme diseaseMiceDay 120Beta 1 domainsAlpha 1Equal severityBorrelia burgdorferiMouse IBurgdorferiHuman alpha 1DiseaseSurface proteins
1994
Target Imbalance: Disparity of Borrelia burgdorferi Genetic Material in Synovial Fluid from Lyme Arthritis Patients
Persing D, Rutledge B, Rys P, Podzorski D, Mitchell P, Ree K, Liu B, Fikrig E, Malawista S. Target Imbalance: Disparity of Borrelia burgdorferi Genetic Material in Synovial Fluid from Lyme Arthritis Patients. The Journal Of Infectious Diseases 1994, 169: 668-672. PMID: 8158048, DOI: 10.1093/infdis/169.3.668.Peer-Reviewed Original ResearchConceptsLyme arthritisClinical specimensLyme arthritis patientsUnderlying pathogenetic mechanismsPolymerase chain reaction studiesSynovial fluid specimensB. burgdorferi infectionArthritis patientsSynovial inflammationPathogenetic mechanismsBurgdorferi infectionPhysiologic imbalanceSynovial fluidFluid specimensEtiologic agentLate manifestationLyme diseaseCultured organismsBorrelia burgdorferiArthritisPatientsDNA reactivityAnalytic sensitivity
1993
OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection
Fikrig E, Barthold SW, Flavell RA. OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection. Infection And Immunity 1993, 61: 2553-2557. PMID: 8500891, PMCID: PMC280883, DOI: 10.1128/iai.61.6.2553-2557.1993.Peer-Reviewed Original ResearchConceptsBooster injectionComplete Freund's adjuvantVaccination of miceMurine Lyme borreliosisMurine Lyme arthritisFinal booster injectionCommencement of vaccinationNumber of miceSurface protein APostexposure immunizationOuter surface protein APostexposure vaccinationLyme arthritisFreund's adjuvantActive immunizationHeart diseaseC3H miceIncomplete adjuvantVaccinationInfectionLyme borreliosisResolution phaseMiceAdjuvantBorrelia burgdorferi